Registration Dossier
Registration Dossier
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EC number: 257-473-3 | CAS number: 51851-37-7
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Bacterial mutagenicity: negative with and without metabolic activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535 or TA 1537 (OECD Test Guideline 471; Hüls, 1997, reliability 2). The range of strains does not comply with current guidelines, therefore, data are read-across from [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS 73609-36-6) which is negative with and without metabolic activation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 (OECD Test Guideline 471; LPT, 2002, reliability 1).
Mammalian cytogenicity: negative with and without metabolic
activation in Chinese hamster V79 cells (OECD Test Guideline 473;
Eurofins Biopharma, 2016a, reliability 1).
Mammalian mutagenicity: negative with and without metabolic
activation in mouse lymphoma L5178Y cells (OECD Test Guideline 490;
Eurofins Biopharma, 2016b, reliability 1).
These studies were conducted in compliance with GLP.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1997-03-13 to 1997-03-24
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- The range of strains does not comply with the current guideline.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1983
- Deviations:
- yes
- Remarks:
- only 4 strains used
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital and Beta-Naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- Plate incorporation (+ / - MA) 50, 160, 500, 1600, 5000 µg/plate
Pre-incubation (+ / - MA) 50, 160, 500, 1600, 5000 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: It is assumed by the reviewer that the solvent was chosen for its solubility properties and relative non-toxicity to bacteria - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- TA 98 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 100, TA 1535 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA 1537 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- All strains (with activation)
- Details on test system and experimental conditions:
- ACTIVATION: One part of S9 fraction was mixed with 9 parts of a cofactor solution resulting in the following mixture: 10% S9 fraction, 22 mM KCl, 5 mM glucose-6-phosphate, 4mM NADP, 100 mM Na2HPO4/NaH2PO4 (pH 7.4), 8 mM MgCl2
APPLICATION: plate incorporation; pre-incubation
DURATION
- Preincubation period: 30 minutes at 30°C with gentle agitation
- Exposure duration: 72 hours at 37°C
NUMBER OF REPLICATIONS: triplicate plates, experiment repeated. Initial experiment used plate incorporation method, the repeat used pre-incubation.
SELECTION AGENT (mutation assays): histidine-deficient agar
DETERMINATION OF CYTOTOXICITY: condition of bacterial lawn/reduction in number of revertants - Evaluation criteria:
- For a test compound to be considered positive, it must (in two independent experiments) cause at least a doubling in the mean revertants per plate of at least one tester strain. This increase must be accompanied by a dose response towards increasing concentrations of the test article.
- Statistics:
- For all replicate platings, the mean number of revertants per plate and the standard deviation around the mean were calculated.
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Conclusions:
- Interpretation of results: negative with and without metabolic activation
[2-(Perfluorohexyl)ethyl]triethoxysilane has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD Guideline 471, compliant with GLP. The range of strains does not comply with the current guideline. No evidence of a test-substance related increase in the number of revertants was observed in Salmonella typhimurium strains TA 98, TA 100, TA 1535 or TA 1537 when tested with or without metabolic activation in the initial plate incorporation assay or the repeat preincubation experiment up to cytotoxic/limit concentrations. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015-08-27 to 2016-01-13
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Version / remarks:
- 2014
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: minimum essential medium (MEM)
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital (80 mg/kg bw) and β-naphthoflavone (100 mg/kg bw) induced rat liver S9
- Test concentrations with justification for top dose:
- Experiment I:
20, 50, 100 and 200 μg/mL without metabolic activation
50, 100, 200 and 500 μg/mL with metabolic activation
Experiment II:
100, 200 and 500 μg/mL without metabolic activation - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: According to the solubility test, the test item was soluble in ethanol. The solvent was compatible with the survival of the cells and the S9 activity. - Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
ACTIVATION: S9 supernatant was mixed with S9 co-factor solution to result in a final protein concentration of 0.75 mg/mL in the cultures. The co-factors added were: 8 mM MgCl2, 33 mM KCl, 5 mM Glucose-6-phosphate, 5 mM NADP in 100 mM sodium-phosphate-buffer pH 7.5.
DURATION
- Exposure duration:
Experiment I: 4 hours, with and without metabolic activation
Experiment II: 21 hours, without metabolic activation
- Expression time (cells in growth medium): Experiment I, 16 +/- 2 hours with and without metabolic activation
- Fixation time (start of exposure up to fixation or harvest of cells): 21 hours after start of exposure
SPINDLE INHIBITOR (cytogenetic assays): Colcemid (0.2 μg/mL culture medium) was added to the cultures about 2.5 hours before preparation of the cells
STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: duplicate cultures
NUMBER OF CELLS EVALUATED: 300 metaphases per concentration were scored for chromosome analysis
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index and relative increase in cell count (RICC) (%)
OTHER EXAMINATIONS:
- Determination of polyploidy: yes - Evaluation criteria:
- The result is considered positive when:
- at least one of the test concentrations exhibits a statistically significant increase compared to the concurrent negative control
- the increase is dose-related when evaluated with an appropriate trend test
- any of the results are outside the distribution of the historical negative control data - Statistics:
- Fisher´s exact test was used to verify the results in the experiment
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation:
Experiment I: at 100 μg/mL and higher without metabolic activation, and at 200 μg/mL and higher with metabolic activation
Experiment II: at 500 μg/mL without metabolic activation - Conclusions:
- Interpretation of results: negative with and without metabolic activation
[2-(Perfluorohexyl)ethyl]triethoxysilane has been tested for ability to cause chromosome aberrations in Chinese hamster V79 cells according to OECD TG 473 and in compliance with GLP (Eurofins BioPharma, 2016). No increase in the number of cells with aberrations was observed either with or without metabolic activation when tested up to precipitating concentrations. Appropriate solvent, negative (treatment medium) and positive controls were included and gave the expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study. - Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016-03-21 to 2016-04-12
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 490 (In vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene) 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Thymidine Kinase (TK) Locus
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI 1640 complete medium
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically "cleansed" against high spontaneous background: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital/ β-naphthoflavone induced rat liver S9
- Test concentrations with justification for top dose:
- 0.05, 0.10, 0.25, 0.50, 1.00, 1.50, 1.75 and 2.0 mg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Ethanol
- Justification for choice of solvent/vehicle: The solvent used was chosen based on the results of the solubility test. - Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol 0.5% v/v
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol 0.5% v/v
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- without metabolic activation
- Untreated negative controls:
- yes
- Remarks:
- treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- ethanol 0.5% v/v
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- ACTIVATION: The S9 supernatant was mixed with S9 cofactor solution to result in final protein concentration of 0.75 mg/mL in the cultures. The cofactors added were: 8 mM MgCl2, 33 mM KCl, 5 mM Glucose-6-phosphate, 5 mM NADP in 100 mM sodium-phosphate-buffer pH 7.4.
METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 hours
- Expression time (cells in growth medium): 2 days at 37 °C
- Selection time (if incubation with a selection agent): 12 days at 37 °C
- Fixation time (start of exposure up to fixation or harvest of cells):
SELECTION AGENT (mutation assays): selective medium with TFT
NUMBER OF REPLICATIONS: duplicate cultures were used
NUMBER OF CELLS EVALUATED:
DETERMINATION OF CYTOTOXICITY
- Method: relative cloning efficiency (RCE); relative total growth (RTG)
OTHER EXAMINATIONS:
- clastogenicity: Colony sizing was performed for the highest concentrations of the test item and for the negative and positive controls. - Evaluation criteria:
- The test item is considered mutagenic if the following criteria are met:
- The induced mutant frequency meets or exceeds the Global Evaluation factor (GEF) of 126 mutants per 10⁶ cells
- A dose-dependent increase in mutant frequency is detected. - Statistics:
- Evaluation of statistical significance (p < 0.05)
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: The pH-values detected with the test item were within the physiological range.
- Precipitation: No precipitation of the test item was noted in the experiment
COMPARISON WITH HISTORICAL CONTROL DATA: All mutant frequencies for negative, solvent and positive controls of the main experiment were found within the historical range of the test facility.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Clastogenicity: none of the obtained values for small colonies exceeded 40% and all dose groups were considered as not clastogenic - Conclusions:
- Interpretation of results: negative with and without metabolic activation
[2-(Perfluorohexyl)ethyl]triethoxysilane has been tested for mutagenicity in mouse lymphoma L5178Y cells according to OECD TG 490, and in compliance with GLP. No test substance induced increase in the number of mutations was observed when tested up to limit concentrations. Appropriate solvent, negative (treatment medium) and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study. - Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2002-05-03 to 2002-08-01
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidine operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor induced rat liver S9
- Test concentrations with justification for top dose:
- 10, 31.6, 100, 316, 1000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Ethylene glycol dimethylether
- Justification for choice of solvent/vehicle: Solubility properties and relative non-toxicity to bacteria - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535, TA 100 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- TA 98 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA 1537 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- TA 102 (without activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-anthracene amide
- Remarks:
- TA 98, TA 102, TA 1537 (with activation)
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- TA 100, TA 1535 (with activation)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium (plate incorporation); preincubation
DURATION
- Preincubation period: 60 minutes
- Expression time (cells in growth medium): 48 hours
NUMBER OF REPLICATIONS: 3 plates for each test concentration; the initial plate incorporation assay was repeated using the pre-incubation method.
DETERMINATION OF CYTOTOXICITY
- Method: Background lawn assessment, relative colony counts
METABOLIC ACTIVATION
Aroclor induced rat liver S9 was tested for protein and P-450 content. S9 mix contained 5% S9, and glucose-6-phosphate and NADP as co-factors. 0.5 ml S9 mix were added to 2 ml top agar, 0.1 ml test material and 0.1 ml cell suspension, giving a final concentration of approximately 1% S9. - Evaluation criteria:
- A result is positive if the number of revertants is significantly increased compared with the solvent control to at least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of the solvent control for TA 1535 and TA 1537 in both experiments.
Positive results have to be reproducible and the histidine independence of the revertants has to be confirmed by streaking on histidine-free agar plates.
Cytotoxicity is defined as a reduction in the number of colonies by >50% compared with the solvent control and/or a sparse background lawn. - Statistics:
- MANN and WHITNEY and Spearman’s rank.
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 316 - 1000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 1000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 1000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 316 - 1000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 316 - 1000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 1000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 316 - 1000 μg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- COMPARISON WITH HISTORICAL CONTROL DATA: Results were within range of historical control data
- Conclusions:
- Interpretation of results: negative with and without metabolic activation
[2-(Perfluorohexyl)ethyl]dichloro(methyl)silane has been tested in a reliable study, conducted according to OECD 471 and in compliance with GLP, no test-substance related increase in the number of revertants was observed with and without metabolic activation when tested up to cytotoxic concentration in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102. The result of the initial plate incorporation assay was confirmed in an independent experiment using the pre-incubation method. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the substance is negative for mutagenicity to bacteria under the conditions of the test.
Referenceopen allclose all
Table 1: Plate incorporation test: revertants per plate (mean of three plates)
Dose/plate (µg) |
TA 98 |
TA 100 |
TA 1535 |
TA 1537 |
||||
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
|
untreated |
30 |
12 |
184 |
133 |
16 |
9 |
18 |
18 |
ethanol |
28 |
17 |
160 |
129 |
9 |
8 |
25 |
15 |
50 |
26 |
15 |
142 |
157 |
16 |
10 |
18 |
16 |
160 |
26 |
12 |
167 |
156 |
16 |
7 |
20 |
15 |
500 |
29 |
16 |
169 |
132 |
13 |
6 |
24 |
13 |
1600 |
27 |
12 |
150 |
119 |
20 |
8 |
21 |
14 |
5000 |
35 |
17 |
175 |
157 |
14 |
9 |
20 |
8 |
positive control (2.5) |
1305 |
110 |
1497 |
- |
189 |
396 |
147 |
- |
positive control (5) |
- |
- |
- |
621 |
- |
- |
- |
- |
positive control (40) |
- |
- |
- |
- |
- |
- |
- |
150 |
Table 2: Preincubation test: revertants per plate (mean of three plates)
Dose/plate (µg) |
TA 98 |
TA 100 |
TA 1535 |
TA 1537 |
||||
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
+ MA |
- MA |
|
untreated |
19 |
16 |
161 |
165 |
14 |
12 |
17 |
19 |
ethanol |
18 |
17 |
151 |
173 |
16 |
10 |
13 |
14 |
50 |
18 |
16 |
143 |
175 |
13 |
9 |
8 |
20 |
160 |
15 |
13 |
142 |
139 |
13 |
7 |
15 |
16 |
500 |
25 |
19 |
161 |
165 |
16 |
10 |
15 |
17 |
1600 |
18 |
11 |
161 |
149 |
14 |
11 |
13 |
15 |
5000 |
22 |
17 |
163 |
170 |
18 |
12 |
16 |
13 |
positive control (2.5) |
1189 |
103 |
1586 |
- |
234 |
440 |
163 |
- |
positive control (5) |
- |
- |
- |
682 |
- |
- |
- |
- |
positive control (40) |
- |
- |
- |
- |
- |
- |
- |
153 |
Table 1: Summary, experiment I and II, with and without metabolic activation
|
Dose Group |
Concentration µg/mL |
Relative Mitotic Index (%) |
RICC (%) |
Mean % Aberrant Cells |
Historical Laboratory Negative Control Range |
Precipitation |
||
Including Gaps |
Excluding Gaps |
||||||||
Experiment I and II, without metabolic activation |
|||||||||
Experiment I 4 hour treatment, 21 hour preparation interval |
C |
0 |
100 |
105 |
4.0 |
2.0 |
0.0% - 4.0 % aberrant cells |
- |
|
S |
0 |
100 |
100 |
3.3 |
1.7 |
- |
|||
3 |
20 |
101 |
94 |
2.3 |
0.3 |
- |
|||
4 |
50 |
95 |
105 |
4.3 |
1.3 |
- |
|||
5 |
100 |
101 |
89 |
1.7 |
1.0 |
+ |
|||
6 |
200 |
99 |
100 |
2.3 |
1.7 |
+ |
|||
EMS |
900 |
117 |
120 |
9.7 |
8.3 |
- |
|||
|
|||||||||
Experiment II 21 hour treatment, 21 hour preparation interval |
C |
0 |
99 |
119 |
1.7 |
0.3 |
0.0 % - 4.0 % aberrant cells |
- |
|
S |
0 |
100 |
100 |
3.3 |
2.0 |
- |
|||
4 |
100 |
101 |
110 |
3.3 |
1.7 |
- |
|||
5 |
200 |
105 |
93 |
2.3 |
1.0 |
- |
|||
6 |
500 |
109 |
92 |
1.7 |
0.7 |
+ |
|||
EMS |
400 |
78 |
78 |
12.3 |
9.0 |
- |
|||
Experiment I, with metabolic activation |
|||||||||
Experiment I 4 hour treatment, 21 hour preparation interval |
C |
0 |
109 |
114 |
2.3 |
1.0 |
0.0 % - 4.3 % aberrant Cells |
- |
|
S |
0 |
100 |
100 |
1.3 |
0.7 |
- |
|||
3 |
50 |
106 |
99 |
1.7 |
1.0 |
- |
|||
4 |
100 |
80 |
77 |
5.7 |
1.7 |
- |
|||
5 |
200 |
91 |
82 |
2.7 |
1.0 |
+ |
|||
6 |
500 |
74 |
79 |
1.7 |
1.0 |
+ |
|||
CPA |
1.5 |
98 |
150 |
8.7 |
7.3 |
- |
|||
C: Negative Control (Culture Medium)
S: Solvent Control (EtOH 0.5 % v/v)
EMS: Ethylmethanesulfonate
CPA: Cyclophosphamide
+ : With precipitation
- : Without precipitation
Table 1: Main Experiment results, without metabolic activation
|
Test Group |
Concentrations µL/ml |
RCE % |
RTG % |
MF (mutants/106cells) |
IMF (mutants/106cells) |
GEF exceeded |
Statistical Significant Increase |
Experiment: without metabolic activation |
C1 |
0 |
117.3 |
118.1 |
114.7 |
/ |
/ |
- |
C2 |
0 |
93.8 |
95.6 |
/ |
/ |
- |
||
S1 |
0 |
100.0 |
100.0 |
100.9 |
/ |
/ |
- |
|
S2 |
0 |
/ |
/ |
- |
||||
3 |
0.05 |
105.3 |
87.1 |
113.9 |
13.0 |
- |
- |
|
4 |
0.10 |
86.8 |
77.0 |
111.6 |
10.7 |
- |
- |
|
5 |
0.25 |
95.3 |
93.9 |
95.7 |
-5.2 |
- |
- |
|
6 |
0.50 |
95.3 |
94.6 |
98.1 |
-2.8 |
- |
- |
|
7 |
1.00 |
101.8 |
86.5 |
86.0 |
-14.9 |
- |
- |
|
8 |
1.50 |
93.8 |
86.9 |
142.2 |
41.3 |
- |
+ |
|
9 |
1.75 |
103.6 |
89.0 |
91.2 |
-9.7 |
- |
- |
|
10 |
2.00 |
96.9 |
87.8 |
112.3 |
11.4 |
- |
- |
|
EMS |
300 μg/mL |
73.7 |
59.0 |
857.5 |
756.6 |
+ |
+ |
|
MMS |
10 μg/mL |
61.2 |
43.7 |
492.0 |
391.2 |
+ |
+ |
Table 2: Main Experiment results, with metabolic activation
|
Test Group |
Concentrations µL/ml |
RCE % |
RTG % |
MF (mutants/106cells) |
IMF (mutants/106cells) |
GEF exceeded |
Statistical Significant Increase |
Experiment: with metabolic activation |
C1 |
0 |
99.7 |
89.9 |
112.5 |
/ |
/ |
- |
C2 |
0 |
108.0 |
101.6 |
/ |
/ |
- |
||
S1 |
0 |
100.0 |
100.0 |
132.4 |
/ |
/ |
- |
|
S2 |
0 |
/ |
/ |
- |
||||
3 |
0.05 |
109.8 |
105.0 |
116.8 |
-15.6 |
- |
- |
|
4 |
0.10 |
96.6 |
99.1 |
137.8 |
5.4 |
- |
- |
|
5 |
0.25 |
74.2 |
82.5 |
191.8 |
59.3 |
- |
+ |
|
6 |
0.50 |
113.6 |
119.0 |
141.4 |
9.0 |
- |
- |
|
7 |
1.00 |
83.2 |
82.2 |
152.4 |
20.0 |
- |
- |
|
8 |
1.50 |
117.5 |
129.4 |
110.5 |
-21.9 |
- |
- |
|
9 |
1.75 |
111.7 |
120.5 |
103.2 |
-29.2 |
- |
- |
|
10 |
2.00 |
108.0 |
119.6 |
91.7 |
-40.7 |
- |
- |
|
B[a]P |
2.5 μg/mL |
74.2 |
25.6 |
721.6 |
589.2 |
+ |
+ |
C: Negative Controls
S: Solvent Controls (ethanol)
EMS: Ethylmethanesulfonate [300 μg/mL]
MMS: Methylmethanesulfonate [10 μg/mL]
B[a]P: Benzo[a]pyrene [2.5 μg/mL]
RCE: Relative Cloning Efficiency
RTG: Relative Total Growth
MF: Mutant Frequency
IMF: Induced Mutant Frequency
GEF: Global Evaluation Factor
Table 1: Dose range-finding study. Number of revertants per plate (2 plates)
|
TA100 |
||
Conc. |
Plate 1 |
Plate 2 |
Cytotoxic |
0* |
112 |
115 |
No |
0.316 |
117 |
105 |
No |
1 |
111 |
110 |
No |
3.16 |
126 |
112 |
No |
10 |
101 |
114 |
No |
31.6 |
116 |
121 |
No |
100 |
172 |
181 |
No |
316 |
165 |
173 |
No |
1000 |
132 |
154 |
Yes |
3160 |
0 |
0 |
Yes |
5000 |
0 |
0 |
Yes |
*solvent control with Ethylene glycol dimethylether
Table 2: Experiment 1. Plate incorporation. Number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA102 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
42 |
51.7 |
No |
133 |
158 |
No |
278 |
295 |
No |
10 |
36.3 |
48.7 |
No |
154 |
148 |
No |
274.7 |
273.7 |
No |
31.6 |
34.7 |
53 |
No |
139 |
153.3 |
No |
268.3 |
275 |
No |
100 |
34.3 |
57 |
No |
137.7 |
131.3 |
No |
271.3 |
270 |
No |
316 |
47.7 |
47.3 |
No |
143.3 |
139.3 |
No |
258 |
272.3 |
No |
1000 |
31.3 |
40.3 |
Yes |
131 |
160.7 |
Yes |
286.7 |
267.3 |
Yes |
Positive control |
1145.7 |
1100 |
No |
1194.3 |
1196.3 |
No |
1320 |
1150.3 |
No |
*solvent control with Ethylene glycol dimethylether
Table 3: Experiment 1. Plate incorporation. Number of revertants per plate (mean of 3 plates)
|
TA1535 |
TA1537 |
||||
Conc.µg/plate |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
13 |
15.3 |
No |
6 |
4 |
No |
10 |
13 |
12 |
No |
3.7 |
4.7 |
No |
31.6 |
14.7 |
14 |
No |
3.3 |
5.7 |
No |
100 |
14.3 |
13 |
No |
3 |
2.7 |
No |
316 |
11 |
13 |
No |
3.7 |
4.7 |
No |
1000 |
12 |
16.3 |
No |
4.3 |
3.3 |
No |
Positive control |
1187 |
1189 |
No |
1191.3 |
1241.7 |
No |
*solvent control with Ethylene glycol dimethylether
Table 4: Experiment 2. Preincubation. Number of revertants per plate (mean of 3 plates)
|
TA98 |
TA100 |
TA102 |
||||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
37.3 |
30.7 |
No |
143.7 |
154 |
No |
280.3 |
290.3 |
No |
10 |
31.7 |
30.3 |
No |
187 |
160.7 |
No |
276.3 |
283.7 |
No |
31.6 |
38 |
35.7 |
No |
171.7 |
144.7 |
No |
288.7 |
286.3 |
No |
100 |
35 |
36.3 |
No |
178 |
152 |
No |
283.3 |
281.7 |
No |
316 |
0 |
36 |
Yes |
162.7 |
144.7 |
No |
297.3 |
265 |
Yes |
1000 |
0 |
0 |
Yes |
0 |
0 |
Yes |
0 |
0 |
Yes |
Positive control |
894.3 |
983.7 |
No |
1326.3 |
1333.3 |
No |
1338.3 |
1344.3 |
No |
*solvent control with Ethylene glycol dimethylether
Table 5: Experiment 2. Preincubation. Number of revertants per plate (mean of 3 plates)
|
TA1535 |
TA1537 |
||||
Conc. |
— MA |
+ MA |
Cytotoxic |
— MA |
+ MA |
Cytotoxic |
0* |
13.7 |
13 |
No |
3 |
4.3 |
No |
10 |
13.3 |
13.7 |
No |
3 |
4.7 |
No |
31.6 |
14.3 |
12 |
No |
3 |
3.3 |
No |
100 |
12.3 |
12.3 |
No |
2.3 |
4.3 |
No |
316 |
14.3 |
12 |
Yes |
4 |
4.3 |
Yes |
1000 |
0 |
12.7 |
Yes |
0 |
0 |
Yes |
Positive control |
487.3 |
499.7 |
No |
502 |
503 |
No |
*solvent control with Ethylene glycol dimethylether
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
[2-(Perfluorohexyl)ethyl]triethoxysilane has been tested for mutagenicity to bacteria, in a study which was conducted according to the OECD Test Guideline 471 and in compliance with GLP. The range of strains does not comply with the current guideline. No evidence of a test-substance related increase in the number of revertants was observed in Salmonella typhimurium strains TA 98, TA 100, TA 1535 or TA 1537 when tested with or without metabolic activation in the initial plate incorporation assay or the repeat preincubation experiment up to cytotoxic/limit concentrations. Appropriate positive and solvent controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test (Hüls, 1997, reliability 2).
No data are available for the mutagenicity of [2-(perfluorohexyl)ethyl]triethoxysilane in a strain of bacteria that can detect cross-linking mutagens, so data are read across from the related substance, [2-(perfluorohexyl)ethyl]dichloro(methyl)silane (CAS No. 73609-36-6), which has been tested in a reliable study, conducted according to OECD 471 and in compliance with GLP. No test-substance related increase in the number of revertants was observed with and without metabolic activation when tested up to cytotoxic concentrations in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102. The result of the initial plate incorporation assay was confirmed in an independent experiment using the pre-incubation method. Appropriate positive and solvent controls were included and gave expected results. It is concluded that the substance is negative for mutagenicity to bacteria under the conditions of the test (LPT, 2002, reliability 1).
[2-(Perfluorohexyl)ethyl]triethoxysilane has been tested for ability to cause chromosome aberrations in Chinese hamster V79 cells according to OECD TG 473 and in compliance with GLP . No increase in the number of cells with aberrations was observed either with or without metabolic activation up to precipitating concentrations. Appropriate solvent, negative (treatment medium) and positive controls were included and gave the expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study (Eurofins BioPharma, 2016a, reliability 1).
[2-(Perfluorohexyl)ethyl]triethoxysilane has been tested for mutagenicity in mouse lymphoma L5178Y cells according to OECD TG 490, and in compliance with GLP. No test-substance induced increase in the number of mutations was observed when tested up to limit concentrations. Appropriate solvent, negative (treatment medium) and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the study (Eurofins BioPharma, 2016b, reliability 1).
Read-across justification
Non-testing methods including read-across from surrogate substances are able to provide information on genetic toxicity (REACH Guidance part 07a, R.7.7.3). In the case of genetic toxicity the presence or absence of functional groups that are known to be related to genetic toxicity is considered important, as the presence or absence of reactive groups and molecular substructures is associated with mutagenic and carcinogenic properties of chemicals (Benigni and Bossa, 2006). Consideration is therefore given to the structural similarity, particularly presence or absence of structural alerts for genetic toxicity, when selecting surrogate substances for genetic toxicity endpoints. Additional information is given in a supporting report (PFA 2013aa).
Read-across hypothesis
The hypothesis is that that source (read-across) substances and registration (target) substance have similar systemic toxicological properties because they hydrolyse to similar silanol hydrolysis products, [2-(perfluorohexyl)ethyl]silanetriol and [2-(perfluorohexyl)ethyl]methylsilanediol and the non-silicon products, ethanol and hydrogen chloride. None of the substances or hydrolysis products have structural alerts for genetic toxicity. Based on publically available information, ethanol and hydrogen chloride are not known to contribute to toxicity at the relevant dose levels (OECD, 2004b and 2002), which is discussed further below.
The registered substance, [2-(perfluorohexyl)ethyl]triethoxysilane, hydrolyses at a moderate rate at neutral pH, and rapidly at low pH, with hydrolysis half-lives of approximately 3 hours at 37.5ºC and pH 7, and approximately 13 seconds at 37.5ºC and pH 2. The products of hydrolysis are [2-(perfluorohexyl)ethyl]silanetriol and ethanol.
The read-across substance, [2-(perfluorohexyl)ethyl]dichloro(methyl)silane, hydrolyses very rapidly, with a hydrolysis half-life of approximately 5 seconds at pH 2 and 25°C, at pH 7 and 37.5°C and at pH 2 and 37.5°C. The products of hydrolysis are [2-(perfluorohexyl)ethyl]methylsilanediol and hydrogen chloride.
Read-across justification
(a) Structural similarity of parent substance and silicon-containing hydrolysis products
[2-(perfluorohexyl)ethyl]triethoxysilane and [2-(perfluorohexyl)ethyl]dichloro(methyl)silane are both salines with highly (but not fully) fluorinated hexyl(ethyl) groups attached to the silicon; the registered substance has three ethoxy groups attached to the silicon, the read-across substance has two chlorine groups and one methyl group. Both hydrolyse rapidly to similar silicon-containing hydrolysis products, [2-(perfluorohexyl)ethyl]silanetriol and [2-(perfluorohexyl)ethyl]methylsilanediol. The other hydrolysis products, ethanol and hydrogen chloride, are not expected to contribute to genetic toxicity.
(b) Lack of structural alerts
None of the substances or hydrolysis products has structural alerts for genotoxicity (Benigni et al., 2008).
(c) Lack of genetic toxicity of the non-silicon hydrolysis product.
Hydrogen chloride gave negative results in the most reliable of the bacterial mutagenicity studies. Positive results were obtained in mutagenicity and cytogenicity assays using mammalian cells (OECD, 2002; ECHA disseminated dossier for hydrogen chloride). The positive results were associated with a decrease in pH, and it is considered that the positive results were likely to have been caused by reduced pH. Positive results caused by high or low pH effects are considered not to be relevant for in vivo situations (ECHA guidance Chapter R.07a), and testing should be carried out at neutral pH.
Ethanol is negative in Salmonella typhimurium bacterial mutagenicity assays, up to limit concentrations, including an appropriate 5th strain (TA 102). No evidence for cytogenicity was found in chromosome aberration studies using cultured human lymphocytes or Chinese hamster ovary cells. A mammalian mutagenicity assay using L5178Y cells gave negative results with and without metabolic activation. Ethanol did not induce micronuclei in bone marrow of rats, or chromosome aberrations in rats or hamsters. Ethanol was negative in the most reliable rodent dominant lethal assay (OECD, 2004b).
Benigni et al (2008).The Benigni/Bossa rule base for mutagenicity and carcinogenicity JR Scientific report EUR 23241 EN
OECD (2002): SIDS Initial Assessment Report for SIAM 15, Boston, USA, 22-25 October 2002: hydrogen chloride, CAS 7647-01-0.
OECD (2004b): SIDS Initial Assessment Report for SIAM 19, Berlin, Germany, 19-22 October 2004, Ethanol, CAS 64-17-5.
Justification for classification or non-classification
Based on the available data for [2-(perfluorohexyl)ethyl]triethoxysilane, no classification is required for genetic toxicity according to Regulation (EC) No 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
